The bulk of recent clinical and laboratory studies suggest that cerebellar stimulation is of little or no clinical usefulness for seizure-suppression. Our own results in a small series on monkeys in the past two years, using a model of spontaneous alumina seizures, suggested only modest benefit in response to cerebellar stimulation. To allow more definitive conclusions concerning cerebellar stimulation, we propose to complete this study with addition of more animals during the first 1-2 years of the next grant period. We also propose to test a technique to identify optimal parameters of cerebeller stimulation in the hope that use of such parameters may maximize therapeutic response. The major goal of this proposal concerns an evaluation of locus coeruleus which is believed to influence epileptic activity through liberation of NE terminals widely dispersed through the brain, particularly forebrain cortex and hippocampus. Electrical stimulation of locus coeruleus might be expected to activate release of NE and thereby inhibit epileptic discharge. To test this hypothesis, a series of experiments involving chronic intermittent stimulation of locus coeruleus is proposed, using an alumina model of chronic focal epilepsy, and a separate model of chronic temporal lobe (psychomotor) epilepsy in awake monkeys. During the first year of the project, a small pilot study will be undertaken to measure metabolites of the biogenic amines in CSF specimens obtained from the monkeys to determine whether there may be correlations with stimulation of cerebellum or locus coeruleus.